This is an R-21 submission that responds to the need for translational research initiatives to apply basic science advances to clinical problems. The project would bring together a team of experienced basic scientists who are experts in hormones, behavior, and development with clinical researchers who study two different clinical syndromes at different levels of analysis. The clinical domains were selected for their distinctly different sex-risk profiles, and because for each domain hormone modulation of the disorder's behavioral expression has been hypothesized but not well-investigated: attention-deficit hyperactivity disorder (ADHD) and eating disorders (EDs). The team would also include expertise in animal models of learning, attention, and cognition, so that component mechanisms underlying behavioral expression can be examined. The team also includes expertise in hormone studies of psychiatric populations with depression. Expertise is also present in environmental hormone disrupting chemicals that are suspected by many scientists of altering cognitive and physical development in subtle ways. Thus, the team will have broad expertise that is designed to foster novel cross-cutting translational research planning and prioritizing in order to foster development of a coherent translational research agenda that can examine the contribution of hormones and hormone disruptors and neuromodulators to sex differences in behavioral expression of psychopathology in multiple domains. Regular meetings of this broadly composed team would be held to assure development of this agenda. In addition, under the award, key pilot studies will be conducted to examine (a) circulating hormonal correlates of cognitive and behavioral functioning in children, adolescents, and young adult males and females with ADHD, (b) hormone moderation of pubertal changes in eating disorder symptoms in a non-clinical human sample expected to be free of dietary disruption of hormonal status, (c) cognitive and affective correlates of background contaminant (PCB and DDE) exposures in clinical and non-clinical human samples using executive function probes not previously applied to this question, and (d) key animal experiments to evaluate whether hormonal effects can explain previously-observed sex differences in learning in animal models of ADHD. Expected outcomes of the award are knowledge about the feasibility and areas of greatest promise for these novel research directions, accompanied by a coherent translational research agenda that can culminate in additional cross-cutting research initiatives.